A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Glutamic acid hydrochloride

Ganciclovir

About this trial

This is an interventional treatment trial for Colitis focused on measuring Intestinal Absorption, Ganciclovir, Drug Therapy, Combination, Cytomegalovirus Infections, Colitis, Administration, Oral, Acquired Immunodeficiency Syndrome, Biological Availability, Glutamic Acid

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Recommended: PCP prophylaxis. Allowed: Antiretroviral therapy during induction and pharmacokinetic part of study, provided patient remains on the same antiretroviral therapy for the duration of the study. Chemotherapy for Kaposi's sarcoma, provided patient is hematologically stable for at least 30 days prior to study entry. Recombinant human erythropoietin. GM-CSF and G-CSF. Other medications necessary for patient's welfare, at the physician's discretion. Patients must have: HIV infection. Biopsy-proven cytomegalovirus (CMV) colitis. Life expectancy of at least 3 months. No active AIDS-defining opportunistic infection requiring therapy that is known to cause nephrotoxicity or myelosuppression. NOTE: Kaposi's sarcoma is permitted if patients are hematologically stable for at least 30 days prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Other etiologies for diarrhea identified at study entry. PER AMENDMENT 3/14/95: For subjects who have diarrhea - no other etiologies for diarrhea identified within 6 weeks of enrollment. Known hypersensitivity to study drugs. CMV retinitis. Concurrent Medication: Excluded: Acyclovir or probenecid (PER AMENDMENT 3/14/95). Immunomodulators. Biologic response modifiers (other than GM-CSF or G-CSF). Investigational agents, with the exception of treatment IND drugs. Antacids. H2 blockers. Proton pump inhibitors. Foscarnet during induction and pharmacokinetic part of study. Intravenous CMV retinitis maintenance therapy (including ganciclovir) during pharmacokinetic part of study. Nephrotoxic agents. Prior Medication: Excluded within 14 days prior to study entry: Immunomodulators. Biologic response modifiers (other than GM-CSF or G-CSF). Investigational agents, with the exception of treatment IND drugs.

Sites / Locations

Alabama Therapeutics CRS
Ucsf Aids Crs
Washington U CRS
NY Univ. HIV/AIDS CRS
Univ. of Cincinnati CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

NCT ID

NCT00000768

First Posted

November 2, 1999

Last Updated

October 27, 2021

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT00000768

Brief Title

A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients

Official Title

A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

undefined (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

August 1998 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary

To determine the oral bioavailability of three dose levels of oral ganciclovir given with and without glutamic acid hydrochloride in patients with cytomegalovirus (CMV) GI disease, and to compare the bioavailability of these regimens to that of standard intravenous (IV) ganciclovir. Long-term ganciclovir maintenance therapy has been recommended for CMV colitis or esophagitis following induction treatment. Oral ganciclovir is a likely candidate for maintenance because of its possible therapeutic value and ease of administration, but an optimum dose has not been determined. Since oral ganciclovir has a low bioavailability and is more soluble in an acid pH environment, the addition of glutamic acid hydrochloride may enhance gastrointestinal absorption of this drug.

Detailed Description

Long-term ganciclovir maintenance therapy has been recommended for CMV colitis or esophagitis following induction treatment. Oral ganciclovir is a likely candidate for maintenance because of its possible therapeutic value and ease of administration, but an optimum dose has not been determined. Since oral ganciclovir has a low bioavailability and is more soluble in an acid pH environment, the addition of glutamic acid hydrochloride may enhance gastrointestinal absorption of this drug. All patients receive an induction regimen of IV ganciclovir administered twice daily for 21 to 42 (Per Amendment 3/4/95) days. A permanent venous catheter is implanted for the induction therapy. If clinically improved following induction, patients are then randomized to receive one of three doses of oral ganciclovir, given first without and then with oral glutamic acid hydrochloride, every 8 hours until they reach a steady state. PER AMENDMENT 3/14/95: After subjects have reached steady state with oral ganciclovir and glutamic acid hydrochloride then PK samples will be taken. Subjects will continue the dosing regimen they were assigned to (glutamic acid hydrochloride will be added if it resulted in at least 33% increased bioavailability) for up to 12 months or until relapse of CMV GI disease is documented. Subjects will be followed at monthly intervals for safety evaluation and for evidence of CMV GI relapse. Subjects who have clinical symptoms of relapse will undergo repeat endoscopy or colonoscopy to document the relapse.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colitis, HIV Infections

Keywords

Intestinal Absorption, Ganciclovir, Drug Therapy, Combination, Cytomegalovirus Infections, Colitis, Administration, Oral, Acquired Immunodeficiency Syndrome, Biological Availability, Glutamic Acid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Allocation

Randomized

Enrollment

24 (false)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Glutamic acid hydrochloride

Intervention Type

Drug

Intervention Name(s)

Ganciclovir

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria Concurrent Medication: Recommended: PCP prophylaxis. Allowed: Antiretroviral therapy during induction and pharmacokinetic part of study, provided patient remains on the same antiretroviral therapy for the duration of the study. Chemotherapy for Kaposi's sarcoma, provided patient is hematologically stable for at least 30 days prior to study entry. Recombinant human erythropoietin. GM-CSF and G-CSF. Other medications necessary for patient's welfare, at the physician's discretion. Patients must have: HIV infection. Biopsy-proven cytomegalovirus (CMV) colitis. Life expectancy of at least 3 months. No active AIDS-defining opportunistic infection requiring therapy that is known to cause nephrotoxicity or myelosuppression. NOTE: Kaposi's sarcoma is permitted if patients are hematologically stable for at least 30 days prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Other etiologies for diarrhea identified at study entry. PER AMENDMENT 3/14/95: For subjects who have diarrhea - no other etiologies for diarrhea identified within 6 weeks of enrollment. Known hypersensitivity to study drugs. CMV retinitis. Concurrent Medication: Excluded: Acyclovir or probenecid (PER AMENDMENT 3/14/95). Immunomodulators. Biologic response modifiers (other than GM-CSF or G-CSF). Investigational agents, with the exception of treatment IND drugs. Antacids. H2 blockers. Proton pump inhibitors. Foscarnet during induction and pharmacokinetic part of study. Intravenous CMV retinitis maintenance therapy (including ganciclovir) during pharmacokinetic part of study. Nephrotoxic agents. Prior Medication: Excluded within 14 days prior to study entry: Immunomodulators. Biologic response modifiers (other than GM-CSF or G-CSF). Investigational agents, with the exception of treatment IND drugs.

Overall Study Officials: